Catecholamine stress hormones regulate cellular iron homeostasis by a posttranscriptional mechanism mediated by iron regulatory protein: Implication in energy homeostasis

Tapryal Nisha, Vivek G. Vishnu, Chinmay K. Mukhopadhyay

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Adequate availability of iron is important for cellular energy metabolism. Catecholamines such as epinephrine and norepinephrine promote energy expenditure to adapt to conditions that arose due to stress. To restore the energy balance, epinephrine/norepinephrine-exposed cells may face higher iron demand. So far, no direct role of epinephrine/norepinephrine in cellular iron homeostasis has been reported. Here we show that epinephrine/norepinephrine regulates iron homeostasis components such as transferrin receptor-1 and ferritin-H in hepatic and skeletal muscle cells by promoting the binding of iron regulatory proteins to iron-responsive elements present in the UTRs of transferrin receptor-1 and ferritin-H transcripts. Increased transferrin receptor-1, decreased ferritin-H, and increased iron-responsive element-iron regulatory protein interaction are also observed in liver and muscle tissues of epinephrine/norepinephrine-injected mice. We demonstrate the role of epinephrine/norepi-nephrine-induced generation of reactive oxygen species in converting cytosolic aconitase (ACO1) into iron regulatory protein-1 to bind iron-responsive elements present in UTRs of transferrin receptor-1 and ferritin-H. Our study further reveals that mitochondrial iron content and mitochondrial aconitase (ACO2) activity are elevated by epinephrine/norepinephrine that are blocked by the antioxidant N-acetyl cysteine and iron regulatory protein-1 siRNA, suggesting involvement of reactive oxygen species and iron regulatory protein-1 in this mechanism. This study reveals epinephrine and norepinephrine as novel regulators of cellular iron homeostasis.

Original languageEnglish (US)
Pages (from-to)7634-7646
Number of pages13
JournalJournal of Biological Chemistry
Volume290
Issue number12
DOIs
StatePublished - Mar 20 2015
Externally publishedYes

Fingerprint

Iron-Regulatory Proteins
Catecholamines
Epinephrine
Homeostasis
Iron
Hormones
Norepinephrine
Apoferritins
Iron Regulatory Protein 1
Transferrin Receptors
Aconitate Hydratase
Untranslated Regions
Energy Metabolism
Muscle
Reactive Oxygen Species
Acetylcysteine
Liver
Energy balance
Muscle Cells
Small Interfering RNA

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Catecholamine stress hormones regulate cellular iron homeostasis by a posttranscriptional mechanism mediated by iron regulatory protein : Implication in energy homeostasis. / Nisha, Tapryal; Vishnu, Vivek G.; Mukhopadhyay, Chinmay K.

In: Journal of Biological Chemistry, Vol. 290, No. 12, 20.03.2015, p. 7634-7646.

Research output: Contribution to journalArticle

@article{2791d6cec64c432f9f0842335bdca165,
title = "Catecholamine stress hormones regulate cellular iron homeostasis by a posttranscriptional mechanism mediated by iron regulatory protein: Implication in energy homeostasis",
abstract = "Adequate availability of iron is important for cellular energy metabolism. Catecholamines such as epinephrine and norepinephrine promote energy expenditure to adapt to conditions that arose due to stress. To restore the energy balance, epinephrine/norepinephrine-exposed cells may face higher iron demand. So far, no direct role of epinephrine/norepinephrine in cellular iron homeostasis has been reported. Here we show that epinephrine/norepinephrine regulates iron homeostasis components such as transferrin receptor-1 and ferritin-H in hepatic and skeletal muscle cells by promoting the binding of iron regulatory proteins to iron-responsive elements present in the UTRs of transferrin receptor-1 and ferritin-H transcripts. Increased transferrin receptor-1, decreased ferritin-H, and increased iron-responsive element-iron regulatory protein interaction are also observed in liver and muscle tissues of epinephrine/norepinephrine-injected mice. We demonstrate the role of epinephrine/norepi-nephrine-induced generation of reactive oxygen species in converting cytosolic aconitase (ACO1) into iron regulatory protein-1 to bind iron-responsive elements present in UTRs of transferrin receptor-1 and ferritin-H. Our study further reveals that mitochondrial iron content and mitochondrial aconitase (ACO2) activity are elevated by epinephrine/norepinephrine that are blocked by the antioxidant N-acetyl cysteine and iron regulatory protein-1 siRNA, suggesting involvement of reactive oxygen species and iron regulatory protein-1 in this mechanism. This study reveals epinephrine and norepinephrine as novel regulators of cellular iron homeostasis.",
author = "Tapryal Nisha and Vishnu, {Vivek G.} and Mukhopadhyay, {Chinmay K.}",
year = "2015",
month = "3",
day = "20",
doi = "10.1074/jbc.M114.592519",
language = "English (US)",
volume = "290",
pages = "7634--7646",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "12",

}

TY - JOUR

T1 - Catecholamine stress hormones regulate cellular iron homeostasis by a posttranscriptional mechanism mediated by iron regulatory protein

T2 - Implication in energy homeostasis

AU - Nisha, Tapryal

AU - Vishnu, Vivek G.

AU - Mukhopadhyay, Chinmay K.

PY - 2015/3/20

Y1 - 2015/3/20

N2 - Adequate availability of iron is important for cellular energy metabolism. Catecholamines such as epinephrine and norepinephrine promote energy expenditure to adapt to conditions that arose due to stress. To restore the energy balance, epinephrine/norepinephrine-exposed cells may face higher iron demand. So far, no direct role of epinephrine/norepinephrine in cellular iron homeostasis has been reported. Here we show that epinephrine/norepinephrine regulates iron homeostasis components such as transferrin receptor-1 and ferritin-H in hepatic and skeletal muscle cells by promoting the binding of iron regulatory proteins to iron-responsive elements present in the UTRs of transferrin receptor-1 and ferritin-H transcripts. Increased transferrin receptor-1, decreased ferritin-H, and increased iron-responsive element-iron regulatory protein interaction are also observed in liver and muscle tissues of epinephrine/norepinephrine-injected mice. We demonstrate the role of epinephrine/norepi-nephrine-induced generation of reactive oxygen species in converting cytosolic aconitase (ACO1) into iron regulatory protein-1 to bind iron-responsive elements present in UTRs of transferrin receptor-1 and ferritin-H. Our study further reveals that mitochondrial iron content and mitochondrial aconitase (ACO2) activity are elevated by epinephrine/norepinephrine that are blocked by the antioxidant N-acetyl cysteine and iron regulatory protein-1 siRNA, suggesting involvement of reactive oxygen species and iron regulatory protein-1 in this mechanism. This study reveals epinephrine and norepinephrine as novel regulators of cellular iron homeostasis.

AB - Adequate availability of iron is important for cellular energy metabolism. Catecholamines such as epinephrine and norepinephrine promote energy expenditure to adapt to conditions that arose due to stress. To restore the energy balance, epinephrine/norepinephrine-exposed cells may face higher iron demand. So far, no direct role of epinephrine/norepinephrine in cellular iron homeostasis has been reported. Here we show that epinephrine/norepinephrine regulates iron homeostasis components such as transferrin receptor-1 and ferritin-H in hepatic and skeletal muscle cells by promoting the binding of iron regulatory proteins to iron-responsive elements present in the UTRs of transferrin receptor-1 and ferritin-H transcripts. Increased transferrin receptor-1, decreased ferritin-H, and increased iron-responsive element-iron regulatory protein interaction are also observed in liver and muscle tissues of epinephrine/norepinephrine-injected mice. We demonstrate the role of epinephrine/norepi-nephrine-induced generation of reactive oxygen species in converting cytosolic aconitase (ACO1) into iron regulatory protein-1 to bind iron-responsive elements present in UTRs of transferrin receptor-1 and ferritin-H. Our study further reveals that mitochondrial iron content and mitochondrial aconitase (ACO2) activity are elevated by epinephrine/norepinephrine that are blocked by the antioxidant N-acetyl cysteine and iron regulatory protein-1 siRNA, suggesting involvement of reactive oxygen species and iron regulatory protein-1 in this mechanism. This study reveals epinephrine and norepinephrine as novel regulators of cellular iron homeostasis.

UR - http://www.scopus.com/inward/record.url?scp=84925310807&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84925310807&partnerID=8YFLogxK

U2 - 10.1074/jbc.M114.592519

DO - 10.1074/jbc.M114.592519

M3 - Article

C2 - 25572399

AN - SCOPUS:84925310807

VL - 290

SP - 7634

EP - 7646

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 12

ER -